Our laboratory is continuing to study the immune response to murine tumors with an emphasis on modeling patient trials based on accurate murine tumor immunotherapy models. Pursuing an avenue utilized in human studies, we have cloned a tumor-specific antigen from the B-16 melanoma utilizing T cells which were therapeutic for that tumor. This antigen proved to be TRP-2, a normal melanocyte differentiation antigen which is closely related to several differentiation antigens identified to be recognized in human melanoma. We have developed reagents for immunizing animals against TRP-2 and have identified the specific peptide epitope in TRP-2 which is being recognized. We are currently pursuing a variety of vaccine approaches in efforts to prevent and treat B-16 melanoma which will serve as models for future human protocols using related antigens. In addition, we have developed a model with the 9873 BALB-C sarcoma in which we have identified the class I restricted antigen which is recognized following whole tumor vaccination, and have introduced the sperm whale myoglobin molecule with a defined class II-presented antigen to serve as a model CD4 cell stimulus. Therefore, this model incorporates completely defined class I and class II restricted antigens to serve as a model for combined vaccine studies in humans. Clinically, the randomized 3-arm trial comparing subcutaneous IL-2 versus high and low-dose intravenous IL-2 in the treatment of metastatic renal cell cancer continues. We have now randomized approximately 250 patients in this trial, and plans are to continue to full accrual. In addition, several randomized trials for adult soft tissue sarcomas continue. One evaluates use of adjuvant chemotherapy in high-grade extremity sarcoma, and another is evaluating the use of radiotherapy for low-grade sarcomas. This latter trial shows a highly significant improvement in local control with radiotherapy with longer follow-up and Quality of Life issues still being examined.